Imrpoving Outcomes with Chemotherapy in Colorectal Cancer: Current Options, Current Evidence

Kim, Ik Yong

Abstract

The last several years have major advances in chemotherapy treatment for adjuvant and metastatic colorectal cancer. We've come from an overall survival of 6 months in patients treated with best supportive care in the mid 1980s and even in the early 1990s. The use of 5-FU/leucovorin alone generates an overall survival of about 6 months. The addition of irinotecan/oxaliplatin allows patients to live a median of about 15 to 17 months. If we make use of all 3 active drugs, FOLFOX and FOLFIRI in a sequential manner, we'll be able to generate an overall survival of about 20 months. Recently, the addition of molecular therapy, in particular bevacizumab and cetuximab to these cytotoxic drugs has allowed us to break the brick wall that was placed at about 2 years median overall survival in large phase 3 trials in patients with metastatic colorectal cancer. The recent presentations provided further evidence that the standard of care in the treatment of advanced CRC consists of a combination of highly active cytotoxic chemotherapy plus the addition of a biologic agents, For clinical research, investigation of the best therapy for CRC has clearly shifted away from investigating conventional chemotherapy toward the question of how to make best use of all available active agents, particularly the novel biologics. Randomized trials have also shown that preoperative chemoradiation yields higher rates of pathologic complete response and local control, compared with radiotherapy alone. In this article, I review recent trials on preoperative and adjuvant therapy of localized rectal cancer. The roles of newer agents, such as capecitabine, oxaliplatin, and bevacizumab, are also discussed, and other key issues in the treatment of localized rectal cancer are reviewed. The planned phase 3 first-line trial will continue to elucidate the role of the currently available biologics in the treatment of CRC. In this article, the important advances in optimal chemotherapy of colorectal cancer will be summarized and approaches to multidisciplinary treatment decision-making in both adjuvant and metastatic settings will be reviewd.